Fig. 1

The SERPINC1 + 1 frameshift mutation c.1247dupC results in an altered AT C-terminus (p.Ser417LysfsTer48). A Comparison of the C-terminal amino acid sequence of WT (AT) and mutant AT (AT_fs) with amino acid sequence change p.Ser417LysfsTer48 given in gray. The reactive center loop is underlined, the arrowhead indicates the position of the reactive Arg-Ser bond. Cys462, involved in a disulfide bond in AT, is shown in light gray. New Cys residues introduced by the frameshift mutation in AT_fs are underlined. B Exemplary results of SSP-PCR screening for the SERPINC1 c.1247dupC mutation in 358 healthy individuals. Upper row: screening for the WT allele using genomic DNA of a healthy individual (C) and a patient described (P) as controls and three out of 358 healthy individuals (H1, H2, H3). The PCR result for the SERPINC1 WT allele is represented by a 238 bp fragment (c.1247C). Lower row: screening for the c.1247dupC allele. Genomic DNA of a healthy individual (C) and a patient (P) were used as controls. The primer combination for detection of the c.1247dupC allele (239 bp) also amplified the AT_{Cambridge II} allele (c.1246G>T) [12], which was found in three out of 358 healthy individuals (H2 shown as example). H₂O, water control; IC, internal PCR control (434 bp fragment from GH1 gene). C Comparison of partial DNA sequences of SERPINC1 WT (c.1247C), the described frameshift mutation (c.1247dupC) and mutations AT_Charleville (c.1246G>C) [13] and AT_{Cambridge II} (c.1246G>T) [12], which could also possibly be detected. The respectively encoded amino acid sequence is given underneath for orientation. Underlined nucleotides indicate the position of the reverse primer used for detection of the mutant allele; nucleotides highlighted by a gray background indicate the respective mutation. Amino acids highlighted by a dotted background indicate the p.Ser417LysfsTer48 mutation. The Ala416Pro and Ala416Ser exchanges, encoded by the AT_Charleville mutation c.1246G>C [13] and AT_{Cambridge II} mutation c.1246G>T [12], respectively, are highlighted by a gray background